Clinical efficacy analysis of preoperative neoadjuvant chemotherapy with high-dose dense paclitaxel plus cisplatin in Stages IB2, IIA2, IIB cervical cancer in Iran.

PURPOSE OF INVESTIGATION: In Iran, the authors use neoadjuvant chemotherapy (NACT) prior to surgery in cervical cancer due to limited access to the radiotherapy and very prolonged waiting time in accession to radiotherapy. The study was done to analyze the efficacy of the NACT with high dose-dense paclitaxel and cisplatin before radical surgery on cure rate, survival rate, and the progression of free survival rate of bulky tumor of cervical cancer in Stages 1B2, IId A2, and IIB. MATERIALS AND METHODS: Fifty-two patients with cervical cancer in Stages Ib2, IIA2, and IIB were selected, and responding patients to chemotherapy were scheduled to undergo radical hysterectomy and bilateral pelvic lymphadenectomy with or without para-aortic lymphadenectomy. RESULTS: Fifty out of 52 patients with a median age of 50 years were evaluable for clinical response. Thirty-two patients (64%) responded to the NACT including six (12%) with a complete clinical response. There was no statistical relationship between clinical response, tumor stage and size, and parametrical involvement, however, patients with higher grade of tumor, adenocarcinoma or tumor in upper 2/3 of vagina showed a higher probability of no response to chemotherapy. Downstaging after NACT in all stages was statistically significant regarding pathologic findings and clinical response (p = 0.002). Five-year survival was 88% and factors affecting survival and disease-free survival were pathological response and tumor site based on cox-regression analysis. Overall recurrence rate was 20% and tumor size was the only significant relevant factor for recurrence (p = 0.017). CONCLUSION: Combined regimen of chemotherapy in locally advanced cervical cancer proved to be valuable and efficacious without any late complications.

Opportunities of marker-assisted selection for rice fragrance through marker-trait association analysis of microsatellites and gene-based markers.

Developing fragrant rice through marker-assisted/aided selection (MAS) is an economical and profitable approach worldwide for the enrichment of an elite genetic background with a pleasant aroma. The PCR-based DNA markers that distinguish the alleles of major fragrance genes in rice have been synthesised to develop rice scent biofortification through MAS. Thus, the present study examined the aroma biofortification potential of these co-dominant markers in a germplasm panel of 189 F2 progeny developed from crosses between a non-aromatic variety (MR84) and a highly aromatic but low-yielding variety (MRQ74) to determine the most influential diagnostic markers for fragrance biofortification. The SSRs and functional DNA markers RM5633 (on chromosome 4), RM515, RM223, L06, NKSbad2, FMbadh2-E7, BADEX7-5, Aro7 and SCU015RM (on chromosome 8) were highly associated with the 2AP (2-acetyl-1-pyrroline) content across the population. The alleles traced via these markers were also in high linkage disequilibrium (R(2) > 0.70) and explained approximately 12.1, 27.05, 27.05, 27.05, 25.42, 25.42, 20.53, 20.43 and 20.18% of the total phenotypic variation observed for these biomarkers, respectively. F2 plants harbouring the favourable alleles of these effective markers produced higher levels of fragrance. Hence, these rice plants can be used as donor parents to increase the development of fragrance-biofortified tropical rice varieties adapted to growing conditions and consumer preferences, thus contributing to the global rice market.

Pharmacological inhibition of forskolin-stimulated adenylate cyclase activity in rat brain by melatonin, its analogs, and diazepam.

Preincubation of rat forebrain membranes for 30-60 min with micromolar concentrations of the pineal hormone, melatonin, significantly inhibited forskolin-stimulated adenylate cyclase (AC) activity. Melatonin had an EC25 (concentration which inhibited AC activity by 25%) of 600 microM and caused a maximal inhibitory effect of approximately 30% at a concentration of 1000 microM. A comparison of the effects of melatonin and its analogs, 6-chloromelatonin and 2-iodomelatonin, in the striatum revealed that these halogenated drugs were 2-3 times more potent than melatonin in inhibiting AC activity. The EC25 values were 611, 226 and 189 microM for melatonin, 6-chloromelatonin and 2-iodomelatonin respectively. The receptor antagonists phentolamine (alpha-adrenergic), propranolol (beta-adrenergic), and metergoline (serotonergic) did not block the effect of melatonin in forebrain membranes. The central-type benzodiazepine (BZ) antagonist, Ro 15-1788 (flumazenil), also failed to block the inhibitory effects of melatonin, and the benzodiazepines, diazepam and Ro 5-4864, on AC activity. Evidence that inhibition of adenylate cyclase activity may be involved in the prevention of seizures suggests that the reported anticonvulsant effect of large doses of melatonin may be due to this mechanism. The greater potency of the halogenated melatonin analogs in inhibiting AC suggests that further study of their potential usefulness as anticonvulsants would be worthwhile.